Molecularly imprinted polymers for cell recognition and immobilization

Christos Galanos,a Karsten Haupta,b
a Université de Technologie de Compiègne, France
b Institut Universitaire de France


Molecular Imprinting is a versatile technology that allows encoding a molecular memory in synthetic polymers, subsequently referred to as molecularly imprinted polymers (MIPs). MIPs are custom-designed receptors materials characterized by their inherent affinity and selectivity for specific target molecules, exhibiting comparable binding properties to natural biological such as antibodies, enzymes, or hormones receptors.

Advantages of MIPs

MIPs, due to their synthetic nature exhibit superior physical robustness, high thermal and pressure resistance, and enhanced tolerance to adverse environment conditions, compared to their biological counterparts.  Furthermore, MIPs offer cost-effective synthesis, facile engineering to meet specific requirements and extend shelf life.

Applications of MIPs

These remarkable characteristics have allowed MIPs to be applied in a wide range of fields including general analytical chemistry, chemical sensor, chromatography separation, sample preparation applied to food safety, environmental analysis, security and defence, or industrial process control. They can also be used for drug screening or in the form of bioactive materials as pharmaceuticals and in cosmetics. 

Targets of MIPs

MIPs are designed to selectively recognize and bind molecular targets, ranging from small organic molecules and ions via biomacromolecules such as proteins, to larger entities such as viruses and cells, based on their size, shape, and chemically functionality.

Synthesis of MIPs

MIPs are produced using a templating process in which functional monomers are organized around the target molecule of interest, either through covalent or non-covalent interactions, forming what is known as the pre-polymerization complex as illustrated in Figure 1. Polymerization with a cross-linking monomer allows freezing the geometry of the 3D polymer network, so that upon removal of the template, cavities complementary in size, shape and arrangement of functional groups are revealed.

Fig. 1: The fundamental principle of molecular imprinting involves the gathering of functional monomers (M) around a template molecule (T). This is followed by a polymerization process in the presence of a cross-linker (CL) (1,2). As a result, a three-dimensional polymer structure is created, featuring distinct imprinted sites. The template molecule is then removed (3), releasing binding cavities capable of selectively identifying and binding the target molecule

MIPs for cell recognition

The synthesis of MIPs for targeting a cell faces challenges that are considerably grater than those for small molecules, due to their large size and complexity. Possible approaches are either the imprinting of the whole cell for example by microcontact printing molding techniques or the imprinting of cell membrane molecules (e.g., proteins, lipids and glycans).

Whole cell is a taxing strategy because many factors such as large size, fragility, complex membrane structure and fluidity need to be considered. In any case, this approach will in most cases create merely shape-specific imprints, rather than binding sites with exactly complementary binding site functionality (Figure 1).

More recent developments rather the imprinting of a cell membrane molecule, or, in analogy to biological antibodies, on the imprinting of an epitope thereof. Indeed, small parts of a target protein, such as a surface accessible peptide called “epitope” in the antibody word, have been proposed as templates, a MIP, which will then be capable for recognizing the cell surface protein molecule, and thus the cell. In fact, the use as templates of chemically synthesized peptides eliminates some issues associated with the molecular imprinting of whole proteins, the presence of numerous functional groups, and cost.

MIPs in the FuturoLEAF project

Our contribution to FuturoLEAF involves the use of molecularly imprinted polymers to selectively capture and immobilize cells on the nanocellulose substrates. Thereby, the utilization of the MIP serves a dual purpose. First, it aims to identify and immobilize the target cell, seamlessly integrating it into the nanocellulose matrix. Second, it will yield a directed immobilization of the cells, which, combined with the inherent properties of the cellulose matrix, is expected to enhance their culturing conditions. This enhancement it anticipated to prolong the lifespan of the cell culture, consequently leading to increase product synthesis. Moreover, this approach is poised to mitigate challenges, such as light penetration and nutrient utilization encountered in suspension cultures.